DOWN-REGULATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CASCADE IMMEDIATELY BEFORE PARTURITION IN THE RAT MYOMETRIUM

OBJECTIVE: This study tested the hypothesis that mitogen-activated pro tein kinase (MAPK) pathway is up-regulated during the course of pregna ncy concomitant with uterine hypertrophy. METHODS: The expression and intracellular distribution of components of the MAPK cascade and the a ctivation of MAPKs erk1 and erk2 were examined in the pregnant rat myo metrium (days 10-22 of gestation). Protein expression was detected by Western analysis of myometrial subcellular fractions. Mitogen-activate d protein kinase activation was studied by detection of tyrosine phosp horylation of erk1 and erk2 kinases and enzymatic activity. RESULTS: M itogen-activated protein kinase activity increased from day 15 to day 20 of pregnancy. Immediately before parturition, MAPK activity, but no t expression, declined sharply. During the same interval, membrane exp ression of the mitogenic-switching protein ras and the ras activator s os declined. CONCLUSION: The shift in intracellular distribution ras a nd ras chaperone proteins may precede the down-regulation of membrane- dependent mitogenic signaling and uterine hypertrophy as pregnancy app roaches parturition. Copyright (C) 1998 by the Society for Gynecologic Investigation.